Background Type 2 diabetes mellitus (T2DM) is a condition characterized by insulin resistance and progressive failure of the insulin-secreting beta-cells. Based on studies in small cohorts of young patients (especially Pima Indian offspring), we know that individuals with childhood onset T2DM are at very high risk for diabetes-related morbidity and mortality, due to a longer life-time duration of diabetes, as well as possible increased rapidity of beta-cell failure. Our primary study objective is to acquire data on the natural history of T2DM in youth. Measurements will include indices of beta-cell function, body composition, cardiovascular disease risk factors, gut hormones, and psychological well-being. These data will be compared to findings in non-diabetic volunteers who are lean or overweight/obese. Data from several recent epidemiologic studies have indicated a link between diet soda consumption, obesity, and even type 2 diabetes. However, there is no evidence for a causal relationship. Artificial sweeteners have long been regarded as metabolically inert substances since they contain no or very few calories. Yet, data from rodent studies show that artificial sweeteners may have distinct effects on glucoregulatory hormones and our previous pilot study has confirmed a greater responsiveness of GLP-1 when a glucose meal was preceded by diet soda. We plan to further characterize effects of consumption of artificial sweeteners on intestinal and will enroll healthy volunteers, as well as subjects with type 1 and type 2 diabetes. These subjects will undergo repeated oral glucose tolerance tests or mixed meal tests, preceded by consumption of a water or a sucralose-containing diet soda. We will investigate differences in insulin, glucose, or other hormone levels between the repeated tests.